DESCRIPTION: (Verbatim from the Applicant's Abstract) There is growing evidence to suggest that schizophrenia is a neurobehavioral disorder that affects fronto-temporal areas of the brain. A relatively neglected, but in many ways ideal, probe of the fronto-limbic system is olfaction. Olfactory processing is mediated by limbic structures implicated in the pathophysiology of schizophrenia. The olfactory system is unique in that only one synapse lies between peripheral receptors and sensory cortex, providing one of the most direct links between the brain and environment. Patients with schizophrenia have significant olfactory deficits. Unlike the relatively static pattern of cognitive deficits seen over the course of illness, though, olfactory abilities appear to decline in linear fashion, independent of normal aging and gender effects. However, family studies have also demonstrated marked deficits in olfactory identification in unaffected first-degree relatives of schizophrenic probands. It would seem, therefore, that olfactory brain regions are affected by genetically-mediated developmental, as well as neurodegenerative processes. In this project, we will investigate the physiological and anatomical correlates of olfactory dysfunction, longitudinally, in patients, siblings and controls. We will build on prior psychophysical work to include the integrated assessment of psychophysical, psychophysiological and volumetric measures of olfactory structure and function. We will study 40 patients with schizophrenia, 40- otherwise healthy siblings and 40 unrelated controls. Physiological data will be acquired using a unique and previously unavailable assessment tool, unilateral olfactory event-related potentials (ERPs), with high density electrode arrays and current source and dipole localization analytic methods. Psychophysical olfactory test data and volumetric MRI measurements of olfactory cortical regions and the olfactory bulbs and tracts will also be obtained. All testing will be repeated after a two-year interval, to assess any differential decline in olfactory abilities in the patietns, attributed to their disease state. The relationship of these olfactory measures to clinical, cognitive and affective symptoms will be investigated. Given the relevance of the neural substrate, we anticipate that a comprehensive assessment of olfactory integrity will illuminate important aspects of the neuropathology of schizophrenia and could be especially helpful in distinguishing developmental from degenerative aspects of the disorder.